The main objective of this proposal is to determine the gastrointestinal secretion, distribution, and reabsorption of vitamin D metabolites in man. Using a combination of methods which quantitatively sample both plasma and intestinal fluids in normal man, we have studied the distribution of intravenously administered (26,27-3H)-25-hydroxyvitamin D3, the major intermediary metabolite of vitamin D3. Within 24 hours of isotope injection, one-third of the radioactivity was secreted with the bile into the lumen of the duodenum. Negligible quantities were recovered from feces or urine during this same time interval, thus indicating recycling of biliary radioactivity and an enterohepatic circulation of 25-hydroxyvitamin D3 (25-OH-D3). Using the same clinical investigative study model and methods, we proposed (1) to chemically characterize the biliary metabolic products derived from 25-OH-D3; (2) to determine the influence of alterations in transit time on the plasma kinetics and intestinal handling of 25-OH-D3; (3) to determine size of the intraluminal intestinal pool of 25-OH-D3 by determination of specific activity; and (4) to study role of bile acids in the secretion and reabsorption of 25-OH-D3. These studies will form the basis of conclusions regarding the relative importance of an enterohepatic circulation in the conversion of vitamin D. The hypothesis to be tested is that failure of reabsorption of biliary metabolites of vitamin D is a significant mechanism of the development of vitamin D deficiency and consequent disorders of calcium homeostasis in gastrointestinal disease.